IL-12 directly up-regulates the expression of HLA class I, HLA class II and ICAM-1 on human melanoma cells: A mechanism for its antitumor activity?

Abstract

IL-12 enhances cytolytic activity and proliferation of NK acid T cells, and induces cytokines such as IFN-γ. No direct effects on non-hematopoietic cells have been shown. This study investigates the effects of IL-12 on melanoma cells in vitro. We analyzed 15 melanoma cell cultures and 1 melanoma cell line. Out of 16 samples 13 expressed the β chain of the IL-12 receptor (IL-12Rβ). Preincubation with IL-12 increased the surface levels of human leukocyte antigen (HLA) class I, HLA class II and intercellular adhesion molecule (ICAM)-1 of those cultures with IL-12Rβ expression. The effects of IL-12 on HLA class I could be blocked by an IL-12-neutralizing monoclonal antibody (mAb), but not by an mAb against IfN-γ. Melanoma cells transduced with IL-12 expressed enhanced levels of HLA class I, HLA class II and ICAM-1 compared to controls. Co-incubation of the melanoma cells with allogeneic peripheral blood mononuclear cells (PBMC) resulted in enhanced proliferation and increased production of IL-2 acid IFN-γ after pretreatment with IL-12. IL-12 pretreatment increased the susceptibility of melanoma cells to lysis by prestimulated autologous PBMC. Since IL-12 induced immunocritical surface molecules on melanoma cells, it might be beneficial during immune interventions in melanoma patients.